دورية أكاديمية
Unlocking Catalytic Diversity of a Formate Dehydrogenase: Formamide Activity for NADPH Regeneration and Amine Supply for Asymmetric Reductive Amination
| العنوان: | Unlocking Catalytic Diversity of a Formate Dehydrogenase: Formamide Activity for NADPH Regeneration and Amine Supply for Asymmetric Reductive Amination |
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| المؤلفون: | Artur Maier, Tanja Knaus, Francesco G. Mutti, Dirk Tischler |
| سنة النشر: | 2024 |
| مصطلحات موضوعية: | Biochemistry, Microbiology, Molecular Biology, Biotechnology, Developmental Biology, Computational Biology, Biological Sciences not elsewhere classified, whole cell approach, unlocking catalytic diversity, altered binding conformation, asymmetric reductive amination, 2 , reductive amination, substrate binding, n <, reductive aminase, work broadens, various reactions, substrate specificity, silico docking, nadh regeneration, less effort, formate dehydrogenase, derivatives thereof, cofactors nadh, catalyzed cleavage, cascade set, candida boidinii, aspergillus oryzae, applied enzyme |
| الوصف: | The formate dehydrogenase (FDH) from Candida boidinii is a well-studied and applied enzyme for NADH regeneration in various reactions. As many oxidoreductases require NADPH, FDH mutants were created with shifted cofactor specificity toward NADP + . However, less effort was made to elucidate the substrate specificity for the hydride donors. Here, we report the FDH-catalyzed cleavage of formamide (F) and derivatives thereof into CO 2 and amines, while regenerating the cofactors NADH and NADPH. Wild-type FDH and the NADP + -accepting variant FDH C23S/D195Q/Y196R/Q197N (FDH M5) showed both activity with 10% (v/v) F, N -methylformamide (MF), and N , N -dimethylformamide of 80, 67, and 4.5 mU/mg, and 4.9, 4.7, and 0.5 mU/mg, respectively. In silico docking and molecular dynamics simulation gave insights into substrate binding, indicating an altered binding conformation. NADP + -accepting variants were utilized in a cascade set up for the reductive amination of cyclohexanone by means of reductive aminase from Aspergillus oryzae with MF as hydride and amine donor, thereby reaching conversion rates of 72% in a whole cell approach. This work broadens the applicability of FDHs in biocatalysis. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | unknown |
| العلاقة: | https://figshare.com/articles/journal_contribution/Unlocking_Catalytic_Diversity_of_a_Formate_Dehydrogenase_Formamide_Activity_for_NADPH_Regeneration_and_Amine_Supply_for_Asymmetric_Reductive_Amination/25091702Test |
| DOI: | 10.1021/acscatal.3c05409.s001 |
| الإتاحة: | https://doi.org/10.1021/acscatal.3c05409.s001Test https://figshare.com/articles/journal_contribution/Unlocking_Catalytic_Diversity_of_a_Formate_Dehydrogenase_Formamide_Activity_for_NADPH_Regeneration_and_Amine_Supply_for_Asymmetric_Reductive_Amination/25091702Test |
| حقوق: | CC BY-NC 4.0 |
| رقم الانضمام: | edsbas.8410FCFD |
| قاعدة البيانات: | BASE |
| DOI: | 10.1021/acscatal.3c05409.s001 |
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